Core B was established in 1990 to provide the human material from clinically well characterized patients and control subjects needed to carry out the specific aims of this program project. During the initial two funding cycles activities were focused on the recruitment and characterization of patients with Parkinson's disease (PD) and Alzheimer's disease (AD). This was accomplished by taking advantage of the Parkinson's Disease and Movement Disorders Center (PD & MDC) program that has existed within the University of Pennsylvania's Department of Neurology since 1982 and the more recently established (1990) Memory Disorders Clinic. Patients and control subjects recruited for this Program Project from these two clinical programs are evaluated using standardized assessment protocols and the clinical data is entered into a common database. Preliminary permission for a brain autopsy is obtained for all participating subjects and clinical assessments are repeated semiannually from the time of enrollment until death. The specific aims and methods described in this competitive renewal application represent a continuation of our previous core activities. However, this cycle will focus on the mechanistic role of synuclein in the pathology of PD, the Lewy body variant of AD (LBVAD) and multiple- system atrophy (MSA). Thus, the focus of the Clinical Core has broadened to include the identification, recruitment and clinical characterization of patients with these synucleinopathies. In addition, the Clinical Core will continue to identify, recruit and characterize patients with AD free of extrapyramidal dysfunction and cognitively normal control subjects in order to provide a source of autopsy material for comparison studies. Thus the overarching goal of the Clinical Core remains unchanged from previous cycles of this Program Project. In addition we maintain our interest in assessing the relationship between specific neuropathological changes found in these diseases and selected clinical features such as cognitive impairment, psychosis, and mood alterations.